Several publications are referenced in this application by numerals in parenthesis in order to more fully describe the state of the art to which this invention pertains. Full citations for these references are found at the end of the specification. The disclosure of each of these publications is incorporated by reference herein.
Hair cells are sensory cells that transduce motion into neural signals. In the cochlea, they are used to detect sound waves in the environment and convert them into auditory signals that can be processed in the brain. Loss of receptor hair cells in the cochlea accounts for a significant proportion of hearing impairment in the population (1). This loss can occur as a consequence of viral or bacterial insult, aging, and damage from intense sound or aminoglycoside antibiotics. The generation of replacement hair cells following damage by sound or drugs has been clearly demonstrated in birds (2-4), the chick being the best-studied model for auditory hair cell regeneration (5). New hair cells arise as progeny from an otherwise non-dividing supporting cell population induced to proliferate by the damage (6-12). Functional recovery of hearing accompanies this cellular recovery process (13,14). The signals and pathways responsible for regenerative proliferation are presently unknown. However, evidence in the art indicates that such a regenerative response also occurs in mammals.